A clinical symposium on ethics at the recent American College of Rheumatology scientific sessions explored not only the ethics of physician-pharmaceutical company relationships in the office, clinic, and academia - as well as in educational and medical publication settings - but also the delicate issues surrounding ethics in placebo-controlled clinical trials, starting with informed-consent forms.
The panel was launched by John J. Cush, MD, Clinical Professor of Internal Medicine, University of Texas Southwestern Medical School and Chief of Rheumatology and Clinical Immunology at Presbyterian Hospital of Dallas, who spoke on physician-pharmaceutical relationships.
The discussion took place against a background in the wider society of two important issues: a decreased ability of public funds to support many needed medical educational programs, and corporate and individual greed that has led to an overstepping of the bounds of normal behavior. How can academic medical centers and individual practices provide funds for educating fellows and residents, training office staff, and continuing education for their staff without overstepping such bounds - when pharmaceutical firms are eager to provide support for such educational programs in the form of unrestricted grants that do not allow editorial input from the pharmaceutical companies?
The issue has come to the forefront in recent years in the presence of the enormous wealth of pharmaceutical companies and how that wealth may be used to influence physician prescribing decisions. For example, some pharmaceutical firms spend as much as $8,000 to $13,000 per physician annually on literature, sales representative visits, token gifts, pens, note pads, educational materials, free dinners to provide drug learning opportunities, consultant fees to physicians to be speakers about the benefits of their drug over another. Is there a conflict of interest if the physician accepts such dinner invitations or other benefits from a pharmaceutical firm? Clearly, physicians must do some self-examination when accepting such benefits and be aware of their prescribing practices and undue influence.
In response to the overwhelming presence of the pharmaceutical firms, a variety of organizations have developed and guidelines from existing healthcare organizations have arisen. Indeed, the pharmaceutical industry itself has developed its own set of guidelines for interactions with health care professionals.
Yet Dr. Cush was quick to point out that pharmaceutical firms should certainly not be painted with a black brush. Not only have our patients benefited from their revolutionary drug development, but the companies all provide charitable support of many kinds, including direct free or low cost drugs to indigent patients. It is up to the physician to help assure that patients in need know about and take advantage of those benefits.
The next speaker was David S. Pisetsky, MD, PhD, Professor of Immunology, Chief of the Division of Rheumatology, and Director of the Arthritis Center at the Duke University Medical Center. As Editor of Arthritis & Rheumatism, he was uniquely positioned to speak about ethical issues in medical publishing.
His presentation was particularly focused toward authors, asking them to give full credit to pharmaceutical companies for their role in supporting research reported. Authors do not do so for fear that it will seem that the research is biased toward the source of that support, which may or may not be true. But by not giving credit where credit is due, it looks as if there is something to hide, when there may be none.
It is well known that decreased federal funding has obliged researchers to seek other sources of funds not only for the research itself, but in publishing. Dr. Pisetsky emphasized that one of the editor's roles in article review is to discern any conflict of interest or bias in the research because of financial support. Has the researcher accepted the responsibility to separate the source of support from the actual research? How can the editor be fair to both sides of the question in what is published, i.e. give the reader the full picture? Without providing information on the source of support, there's a piece missing from the puzzle.
The final speaker was Arthur F. Kavanaugh, MD, Director of the Center for Innovative Therapy, Division of Rheumatology, Allergy and Immunology, University of California at San Diego, who discussed ethical issues in clinical trials. The problems that have recently been brought to public attention include the readability of consent forms and the nature of informed consent.
The reading level of most informed consent forms often requires a graduate education. However, various studies suggest that they should probably be aimed at an eighth grade reading level. If we aim higher, then they are not understandable by the patient and we cannot say that the patient has been "informed."
What does informed consent truly mean? Studies have shown that, simply by hearing that they are being offered an opportunity to participate in a research project, patients unfortunately "block out" the part that says they may be receiving a placebo. So no matter what is written on the form or told to them, patients believe they will be getting something that will help their disease. In that psychological setting, how can consent be informed? How can we convince patients that they may not be helped by this clinical trial - because their perceptions may not cohere with reality? Are we coercing people to join trials simply by offering participation?
Indeed, when we know that there are so many drugs on the market that do work for many rheumatic diseases, what is our ethical rationale for continuing to compare new drugs against placebo rather than the current standard of care?
Another ethical issue concerns the trial launched by a pharmaceutical company and then stopped by the firm when it's not going as expected. How should we be taking care of those patients when trials are stopped before completion? The panel raised a wide range of excellent questions, many of which do not have instant answers - and some of which lead to other questions.
For example, in open-ended studies after a drug has been approved, should we not be able to give the approved drug to everyone, rather than continuing control participants on placebo? Do controls understand that some people are still on nothing?
New biologics costs thousands of dollars a year. Some patients get it free in clinical trial. When the trial ends successfully, what happens to patients who then cannot afford to buy it either on their own or through their insurance? Do the recruiting physicians or pharmaceutical company owe any assistance to the participating patients, e.g., leading them to charitable assistance?
Whether in a research project, a medical center, or an office practice, it is clear that the leader sets the guidelines and others - whether the medical staff or the office staff - follow. So physicians are responsible not only for their own behavior but also for those who work for them.
And the bottom line on determining ethical behavior is to think constantly about the issue of how one is behaving - to assess whether we are living our values on a daily basis - and, if in doubt, to ask "Will this yield a benefit to my patient?" If you can answer "Yes" to that question, you are performing in an ethical manner.